The Function And Mechanism Of USP10 Regulating MSI2 In Colon Cancer

Objective: Ubiquitin carboxyl-terminal hydrolase 10(USP10)is a member of the ubiquitinates’ family,and recent studies have shown that USP10 plays a crucial role in tumorigenesis.This study found that USP10 can affect the development of colon cancer by regulating the expression of MSI2,and provided a new theoretical basis for the treatment of colon cancer.Methods: The expression of USP10 and MSI2 in paired samples of colon cancer patients was analyzed by q RT-PCR and Westernblot.Immunofluorescence was used to localize the expression of USP10 and MSI2 in colon cancer cells.The co-immunoprecipitation technique and His pull-down technique were used to verify the stability of USP10 on MSI2 and to explore the specific deubiquitination mechanism.The USP10 and MSI2 were knocked down respectively in LOVO colon cancer cell lines,which were used to detect the effects of function on colon cancer cell lines by CCK-8 assays,plate cloning assays and other experimental methods.And the specific deubiquitination modification of MSI2 by USP10 was verified by replenishing MSI2.Results: Data analyses of paired samples of colon cancer patients by q RT-PCR and Westernblot showed that the protein expression level of MSI2 in colon cancer tissues was correlated with the protein expression of USP10,and both were higher than normal tissues.USP10 is able to interact with MSI2 and the stabilization of USP10 on MSI2 is dose dependent.USP10 modifies MSI2 by specific deubiquitination of ubiquitin by Lys-48.The colon cancer cell lines that knocked down USP10 and MSI2,respectively,significantly reduced their proliferative capacity;Moreover,after replenishing MSI2 in the cell line knocking down USP10,the proliferative capacity was not significantly different from that of the control group.Conclusions: Given the importance of USP10 in the development of colon cancer,we hope to develop USP10 as a therapeutic target for colon cancer in the future.